1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
Download icon

Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis

  1. Kimberly Box
  2. Bradley W Joyce
  3. Danelle Devenport  Is a corresponding author
  1. Princeton University, United States
Research Article
  • Cited 19
  • Views 2,793
  • Annotations
Cite this article as: eLife 2019;8:e47102 doi: 10.7554/eLife.47102

Abstract

The control of cell fate through oriented cell division is imperative for proper organ development. Basal epidermal progenitor cells divide parallel or perpendicular to the basement membrane to self-renew or produce differentiated stratified layers, but the mechanisms regulating the choice between division orientations are unknown. Using time-lapse imaging to follow divisions and fates of basal progenitors, we find that mouse embryos defective for the planar cell polarity (PCP) gene, Vangl2, exhibit increased perpendicular divisions and hyperthickened epidermis. Surprisingly, this is not due to defective Vangl2 function in the epidermis, but to changes in cell geometry and packing that arise from the open neural tube characteristic of PCP mutants. Through regional variations in epidermal deformation and physical manipulations, we find that local tissue architecture, rather than cortical PCP cues, regulates the decision between symmetric and stratifying divisions, allowing flexibility for basal cells to adapt to the needs of the developing tissue.

Data availability

All measured data are reported as their full distributions in the figures and supplements. Source data files with individual measurements are provided for all figures. Matlab codes for data analysis are provided in Source Code File 1.

Article and author information

Author details

  1. Kimberly Box

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Bradley W Joyce

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Danelle Devenport

    Department of Molecular Biology, Princeton University, Princeton, United States
    For correspondence
    danelle@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5464-259X

Funding

National Institutes of Health (R01AR068320)

  • Danelle Devenport

National Institutes of Health (T32GM007388)

  • Kimberly Box

National Institutes of Health (AR8472471)

  • Kimberly Box
  • Danelle Devenport

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures involving animals were approved by Princeton University'sInstitutional Animal Care and Use Committee (IACUC) under protocol #1867. Mice were housed in an AALAC-accredited facility in accordance with the Guide for the Care and Use of Laboratory Animals. This study was compliant with all relevant ethical regulations regarding animal research.

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: March 24, 2019
  2. Accepted: June 12, 2019
  3. Accepted Manuscript published: June 12, 2019 (version 1)
  4. Version of Record published: June 25, 2019 (version 2)

Copyright

© 2019, Box et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,793
    Page views
  • 435
    Downloads
  • 19
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    Jody A Summers, Elizabeth Martinez
    Research Article Updated

    Postnatal ocular growth is regulated by a vision-dependent mechanism that acts to minimize refractive error through coordinated growth of the ocular tissues. Of great interest is the identification of the chemical signals that control visually guided ocular growth. Here, we provide evidence that the pro-inflammatory cytokine, interleukin-6 (IL-6), may play a pivotal role in the control of ocular growth using a chicken model of myopia. Microarray, real-time RT-qPCR, and ELISA analyses identified IL-6 upregulation in the choroids of chick eyes under two visual conditions that introduce myopic defocus and slow the rate of ocular elongation (recovery from induced myopia and compensation for positive lenses). Intraocular administration of atropine, an agent known to slow ocular elongation, also resulted in an increase in choroidal IL-6 gene expression. Nitric oxide appears to directly or indirectly upregulate choroidal IL-6 gene expression, as administration of the non-specific nitric oxide synthase inhibitor, L-NAME, inhibited choroidal IL-6 gene expression, and application of a nitric oxide donor stimulated IL-6 gene and protein expression in isolated chick choroids. Considering the pleiotropic nature of IL-6 and its involvement in many biological processes, these results suggest that IL-6 may mediate many aspects of the choroidal response in the control of ocular growth.

    1. Developmental Biology
    2. Genetics and Genomics
    Juliet R Girard et al.
    Research Article Updated

    Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.